Pyruvate Kinase Deficiency

Erythrocyte pyruvate kinase deficiency (PKD) is a genetic disorder that interferes with the production of energy in the form of ATP in erythrocytes, resulting in a shortened life span of these cells and hemolytic anemia. This condition is caused by a specific mutation in the PKLR gene, detected in several breeds such as Abyssinians, Somalis and others, where its prevalence varies considerably, reaching up to 12.97% in the Bengal breed.

Symptoms

Common clinical signs of the disease include lethargy, weight loss, pale mucous membranes, loss of appetite and jaundice. In addition, blood tests often show anemia with mild to moderate reticulocytosis and hyperbilirubinemia. The severity of symptoms and age of onset vary widely, from one month to five years of age. Some cats may show no significant clinical signs, while others may present with episodes of symptoms related to stressful situations.

Disease Management

Management of the disease focuses on treating clinical signs and improving the quality of life of affected cats, as there is no definitive cure. Strategies include blood transfusions in cases of severe anemia, avoiding stressful situations and controlling secondary infections.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the cat, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected cat must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between cats carrying genetic variants that may cause disease is not recommended, even if they do not show symptoms.

Technical report

Erythrocyte pyruvate kinase deficiency (PKD) is a genetic disorder that affects ATP production in erythrocytes, with pyruvate kinase being crucial for this function in tissues without mitochondria such as mature erythrocytes. Lack of this essential enzyme for glycolysis leads to shortened erythrocyte lifespan and hemolytic anemia. In cats, PKD results from mutations in the PKLR gene, which encodes pyruvate kinase in the liver and erythrocytes. In cats, the causative variant of PKD is a guanine-to-adenine transition in intron 5 of the PKLR gene that causes deletion of 13 bases and results in a truncated, nonfunctional enzyme. This deletion is found in breeds such as Abyssinians and Somalis, and causes a significant decrease in the stability and activity of the enzyme.

Most affected breeds

Abyssinian
Bengal
Caracal
Chausie
Egyptian Mau
European Shorthair
Highlander
Highlander Shorthair
LaPerm
Lykoi
Maine Coon
Longhair Minuet
Munchkin
Neva Masquerade
Norwegian Forest Cat
Pixiebob
Savannah
Singapura
Somali
Toyger

Bibliography

Grahn RA, Grahn JC, Penedo MC, et al. Erythrocyte pyruvate kinase kinase deficiency mutation identified in multiple breeds of domestic cats. BMC Vet Res. 2012 Oct 30